Lagging Brain Gene Expression Patterns of Drosophila melanogaster Young Adult Males Confound Comparisons Between Sexes.

Many species, including fruit flies (Drosophila melanogaster), are sexually dimorphic. Phenotypic variation in morphology, physiology, and behavior can affect development, reproduction, health, and aging. Therefore, designating sex as a variable and sex-blocking should be considered when designing experiments. The brain regulates phenotypes throughout the lifespan by balancing survival and reproduction, and sex-specific development at each life stage is likely. Changes in morphology and physiology are governed by differential gene expression, a quantifiable molecular marker for age- and sex-specific variations. We assessed the fruit fly brain transcriptome at three adult ages for gene expression signatures of sex, age, and sex-by-age: 6698 genes were differentially expressed between sexes, with the most divergence at 3 days. Between ages, 31.1% of 6084 differentially expressed genes (1890 genes) share similar expression patterns from 3 to 7 days in females, and from 7 to 14 days in males. Most of these genes (90.5%, 1712) were upregulated and enriched for chemical stimulus detection and/or cilium regulation. Our data highlight an important delay in male brain gene regulation compared to females. Because significant delays in expression could confound comparisons between sexes, studies of sexual dimorphism at phenotypically comparable life stages rather than chronological age should be more biologically relevant.